chr7-86810424-T-A

Variant names:

• chr7-86810424-T-A
• rs17676277
• NM_000840.3:c.1324+23308T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000840.3(GRM3):​c.1324+23308T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,890 control chromosomes in the GnomAD database, including 2,085 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2085 hom., cov: 32)
• Consequence: GRM3 NM_000840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 4 publications found

Genes affected

GRM3 (HGNC:4595): (glutamate metabotropic receptor 3) L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. [provided by RefSeq, Jul 2008]

GRM3-AS1 (HGNC:40264): (GRM3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM3	NM_000840.3	c.1324+23308T>A		intron_variant	Intron 3 of 5	ENST00000361669.7	NP_000831.2
GRM3	NM_001363522.2	c.1324+23308T>A		intron_variant	Intron 3 of 4		NP_001350451.1
GRM3	XM_047420268.1	c.1324+23308T>A		intron_variant	Intron 4 of 6		XP_047276224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM3	ENST00000361669.7	c.1324+23308T>A		intron_variant	Intron 3 of 5	1	NM_000840.3	ENSP00000355316.2
GRM3	ENST00000439827.1	c.1324+23308T>A		intron_variant	Intron 3 of 4	1		ENSP00000398767.1
GRM3-AS1	ENST00000785213.1	n.167+3753A>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23081 AN: 151772 Hom.: 2085 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.152 AC: 23084 AN: 151890 Hom.: 2085 Cov.: 32 AF XY: 0.147 AC XY: 10899 AN XY: 74260

African (AFR) AF: 0.0743 AC: 3083 AN: 41518

American (AMR) AF: 0.133 AC: 2031 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3464

East Asian (EAS) AF: 0.0259 AC: 134 AN: 5178

South Asian (SAS) AF: 0.0589 AC: 284 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1744 AN: 10558

Middle Eastern (MID) AF: 0.131 AC: 38 AN: 290

European-Non Finnish (NFE) AF: 0.218 AC: 14802 AN: 67834

Other (OTH) AF: 0.164 AC: 344 AN: 2102

Alfa AF: 0.186 Hom.: 371

Bravo AF: 0.146

Asia WGS AF: 0.0540 AC: 189 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.57
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17676277; hg19: chr7-86439740;